It is well established from both animal and human studies that there is a general decrease in immune function that occurs with aging. This project focuses on examining the cause(s) for this decline at the molecular level. Of particular significance is the decline in production of Interleukin 2 (IL-2), a lymphokine absolutely required for the proliferation of certain T cell populations. A primary objective of these studies is to determine whether the decline in IL-2 protein is accompanied by decreased expression of IL-2 mRNA. If so (and preliminary evidence indicates that this is the case), then we will attempt to determine what factors are responsible for the decreased IL-2 mRNA synthesis and whether or not they can be reversed. In addition, these studies will include examination of the expression of two additional genes with aging, both of whose regulation is intimately linked to IL-2. These are the IL-2 receptor and gamma interferon, another lymphokine whose expression is induced by IL-2.